Associations of Adipocytokines with The Development of Cardiovascular Events in Young People.

The research was aimed to study the associations of adipocytokines with the risk of cardiovascular events and to determine the threshold values of adipocytes for the prognosis of cardiovascular events in a young population. MATERIALS AND METHODS: The study is an epidemiological cohort study. The analysis included 1240 people aged 25-44 years. The endpoint was combined and included: death from cardiovascular disease, myocardial infarction, probable myocardial infarction, acute cerebrovascular accident, hospitalization for cardiovascular disease, and revascularization. Adipocytokines were determined with a MILLIPLEX panel. RESULTS: In the examined population, 1.7% of cases of cardiovascular events were detected during cohort observation, of which 28.6% were fatal events. In men, cardiovascular endpoints were recorded 4.3 times more often than in women (17 (81%) vs. 4 (19%), p = 0.003). In individuals with cardiovascular events, arterial hypertension (2.6 times), diabetes mellitus (8.6 times), and overweight/obesity (1.5 times) were more often recorded compared to individuals without cardiovascular events. For tumor necrosis factor-alpha (TNFa), the threshold value was 2.5 pg/mL, with sensitivity assessment (Se) at 85.7% and specificity (Sp) at 83.3%. For amylin, the threshold value was 10.5 pg/mL, with Se at 73.7% and Sp at 67.0%. For pancreatic polypeptide (PP), the threshold value was 43.7 pg/mL, with Se at 85.7% and Sp at 56.7%. CONCLUSION: A method for assessing the risk of cardiovascular events in young people includes determining the levels of amylin, PP, and TNFa in blood serum. The cut-off points for predicting cardiovascular events were levels of amylin above 10.5 pg/mL, PP above 43.7 pg/mL, or a decrease in TNFa below 3.8 pg/mL.

Associations of Adipocytokines and Early Renal Dysfunction in Young People on the Background of Dyslipidemia.

BACKGROUND: There are data supporting the idea that atherogenic dyslipidemia is a risk factor for CKD and reduced GFR. The aim was to evaluate the associations between adipocytokines and early renal dysfunction in young people with dyslipidemia. MATERIALS AND METHODS: A population study was conducted in IIPM-Branch of IC&G SB RAS, in 2013-2017. Furthermore, 1033 people were included in the study (469 men (45.4%) and 564 women (54.6%)). The study included blood sampling, anthropometric data, and adipokines by multiplex analysis. RESULTS: Among people with reduced kidney function and DLP, men were 3.1 times more common than without DLP, women smoked 2 times less often, arterial hypertension was 7.8 times more common, and abdominal obesity was 2.7 times more common (and women with DLP were 3 times more likely than those without DLP). An increase in the level of resistin by 1 mcg/mL was associated with an increased chance of having renal dysfunction by 0.2%. An increase in the level of GIP was associated with an increased chance of having renal dysfunction by 1.1%. CONCLUSIONS: In young people with dyslipidemia, regardless of the presence of abdominal obesity, resistin and GIP are associated with the presence of renal dysfunction.

Adipokine-Cytokine Profile in Patients with Unstable Atherosclerotic Plaques and Abdominal Obesity.

The goal of the research was to study the levels of adipokines and their associations with unstable atherosclerotic plaques in patients with coronary atherosclerosis and abdominal obesity (AO). METHODS: The study included 145 men aged 38-79 with atherosclerosis of the coronary arteries (CA) and stable angina pectoris II-III FC who were hospitalized for coronary bypass surgery (2011-2022). The final analysis included 116 patients. Notably, 70 men had stable plaques in the CA (of which 44.3% had AO), and 46 men had unstable plaques in the CA (of which 43.5% had AO). Adipocytokine levels were determined using multiplex analysis (Human Metabolic Hormone V3 panel). RESULTS: In the subgroup of patients with unstable plaques, patients with AO had a GLP-1 level that was 1.5 times higher and a lipocalin-2 level that was 2.1 times lower, respectively. GLP-1 is direct, and lipocalin-2 is inversely associated with AO in patients with unstable plaques. Among patients with AO, the level of lipocalin-2 in patients with unstable plaques was 2.2 times lower than in patients with stable plaques in the CA. The level of lipocalin-2 was inversely associated with the presence of unstable atherosclerotic plaques in the CA. CONCLUSION: GLP-1 is directly associated with AO in patients with unstable atherosclerotic plaques. Lipocalin-2 is inversely associated with unstable atherosclerotic plaques in patients with AO.

Blood Levels of Indicators of Lower Respiratory Tract Damage in Chronic Bronchitis in Patients with Abdominal Obesity.

OBJECTIVE: to study biomolecules associated with pathology in the respiratory system, in particular, with the development of chronic bronchitis in patients with abdominal obesity. MATERIALS AND METHODS: This is a pilot study. The main group consisted of 158 people with chronic bronchitis, divided into two subgroups: one with abdominal obesity, and the other without it. The control group consisted of 68 people without chronic bronchitis. We determined the blood levels of SP-A, SP-D, α1-antitrypsin, CC16, PARC, and RELM-ß. RESULTS: In the first subgroup, patients significantly more often complained of coughing, experienced shortness of breath 1.5 times more often with light physical exertion and 2.7 times more often with moderate physical exertion. In these patients, a Tiffeneau-Pinelli index (FEV1/FVC) below 70% was 1.8 times more common, more patients had FEV1 and FVC of less than 80%, and presented a statistically significant decrease in SP-A, α1-antitrypsin, CC16 levels and an increase in PARC levels than in the second subgroup. CONCLUSION: In patients with chronic bronchitis and abdominal obesity, there is a decrease in the levels of SP-A, α1-antitrypsin, CC16 and an increase in the level of PARC compared with patients without abdominal obesity, which is probably due to the presence of an additional source of chronic inflammation associated with adipose tissue.

Associations of Antioxidant Enzymes with the Concentration of Fatty Acids in the Blood of Men with Coronary Artery Atherosclerosis.

OBJECTIVE: To identify associations of fatty acids (FAs) with the antioxidant enzymes in the blood of men with coronary atherosclerosis and ischemic heart disease (IHD). METHODS: The study included 80 patients: control group-20 men without IHD, the core group-60 men with IHD. The core group was divided into subgroups: subgroup A-with the presence of vulnerable atherosclerotic plaques, subgroup B-with the absence of vulnerable atherosclerotic plaques. We analyzed the levels of FAs, free radicals, superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) in the blood. RESULTS: Patients with IHD, compared with the control group: (1) had higher levels of SOD, CAT, myristic, palmitic, palmitoleic, and octadecenoic FAs; (2) had lower levels of GPx, α-linolenic, docosapentaenoic, docosahexaenoic, and arachidonic FAs. In subgroup A there were found: (1) negative associations of SOD-with linoleic, eicosatrienoic, arachidonic, eicosapentaenoic, docosapentaenoic and docosahexaenoic FAs, positive associations-with palmitic acid; (2) positive correlations of CAT level with palmitoleic and stearic acids; (3) negative associations between of GPx and palmitic, palmitoleic, stearic and octadecenoic FAs. CONCLUSIONS: Changes in the levels of antioxidant enzymes, and a disbalance of the FAs profile, probably indicate active oxidative processes in the body and may indicate the presence of atherosclerotic changes in the vessels.

Association of Matrix Metalloproteinases with Coronary Artery Calcification in Patients with CHD.

This work is aimed at studying the relationship of matrix metalloproteinases with calcification of the coronary arteries. The study included 78 people with coronary heart disease (CHD) and 36 without CHD. Blood and samples of coronary arteries obtained as a result of endarterectomy were examined. Serum levels of metalloproteinases (MMP) MMP-1, MMP-2, MMP-3, MMP-7, MMP-9, MMP-10, MMP-12, and MMP-13 were determined by multiplex analysis. In blood vessel samples, MMP-1, MMP-3, MMP-7, and MMP-9 were determined by enzyme immunoassay; MMP-9 expression was evaluated by immunohistochemistry. Patients with CHD had higher serum levels of MMP-1, MMP-7, and MMP-12. Blood levels of MMP-1 and MMP-3 were associated with calcium levels, MMP-9 with osteoprotegerin and osteonectin, MMP-7 and MMP-10 with osteoprotegerin, MMP-12 with osteocalcin, and MMP-13 with osteopontin. Calcified plaques had higher levels of MMP-1 and MMP-9 compared to plaques without calcification. The relative risk of coronary arteries calcification was associated with MMP-9, which is confirmed by the results of immunohistochemistry. The results obtained indicate the participation of some MMPs, and especially MMP-9, in the calcification processes. The study can serve as a basis for the further study of the possibility of using MMP-1, MMP-7 and MMP-12 as potential biomarkers of CHD.

The Influence of Calcification Factors and Endothelial-Dysfunction Factors on the Development of Unstable Atherosclerotic Plaques.

BACKGROUND: This study aimed to evaluate changes in markers of calcification and of endothelial dysfunction during the development of calcification and instability of atherosclerotic plaques and to identify associations of calcification factors with the formation of unstable plaques. METHODS: We analyzed 44 male patients with coronary atherosclerosis who underwent endarterectomy in coronary arteries during coronary bypass surgery. The endarterectomy material (intima/media) was examined using histological and biochemical methods, and the stability and calcification degree of atherosclerotic plaques were assessed. In homogenates of the tissue samples and in blood, concentrations of osteoprotegerin, osteocalcin, osteopontin, osteonectin, monocyte-chemoattractant protein type 1 (MCP-1), soluble vascular cell adhesion molecule 1 (sVCAM-1), and E-selectin were determined by enzyme immunoassays. RESULTS: Unstable atherosclerotic plaques proved to be calcified more frequently (80.4% of plaques) than stable ones (45.0%). Osteonectin, E-selectin, and sVCAM-1 levels were lower in unstable plaques and plaques with large calcification deposits. Osteocalcin content increased with the increasing size of the calcification deposits in plaque. Blood osteocalcin concentration directly correlated with osteocalcin concentration in atherosclerotic plaques and was higher in the blood of patients with calcified plaques in coronary arteries. CONCLUSIONS: The results provide the basis for further research on the suitability of osteocalcin as a potential biomarker of an unstable calcified atherosclerotic plaque in a coronary artery.

The Blood Cytokine Profile of Young People with Early Ischemic Heart Disease Comorbid with Abdominal Obesity.

OBJECTIVE: The aim was to study the blood cytokine/chemokine profile of 25-44-year-old people with early ischemic heart disease (IHD) comorbid with abdominal obesity (AO). METHODS: A cross-sectional medical examination of subjects in Novosibirsk, Russia, was conducted after random sampling of the above age group. A total of 1457 subjects, 804 females and 653 males, were analyzed. The epidemiological diagnosis of IHD was made in accordance with 17 validated and functional criteria, employing exercise ECG for confirmation. Simultaneous quantitative analyses of 41 cytokines/chemokines in blood serum were performed by a multiplex assay using the HCYTMAG-60K-PX41 panel (MILLIPLEX MAP) on a Luminex 20 MAGPIX flow cytometer, with additional ELISA testing. RESULTS: Flt3 ligand, GM-CSF, and MCP-1 were significantly associated with the relative risk of early IHD. In the presence of AO, GM-CSF, MCP-1 and IL-4 also significantly correlated with the relative risk of early IHD. By univariate regression analysis, the relative risk of early IHD was associated with lowered blood concentrations of Flt3 ligand, whereas the relative risk of early IHD in the presence of AO was associated with lowered blood concentrations of GM-CSF. Employing multivariable regression analysis, only lower blood levels of Flt3 ligand were associated with a relative risk of early IHD, whereas the relative risk of early IHD in the presence of AO was limited to lower levels of IL-4. CONCLUSION: Findings related to Flt3 ligand, GM-CSF, and IL-4 are consistent with the international literature. Results from the present study are partly confirmative and partly hypothesis generating.

The Short Overview on the Relevance of Fatty Acids for Human Cardiovascular Disorders.

This review presents existing evidence of the influence of saturated and unsaturated fatty acids on cardiovascular diseases (CVD). Data are discussed regarding the roles of the most relevant fatty acids, such as myristic (C14:0), palmitic (C16:0), stearic (C18:0), palmitoleic (C16:1), oleic (C18:1), linoleic (C18:2), α-linolenic (C18:3, ω-3), γ-linolenic (C18:3, ω-6), arachidonic (C20:4), eicosapentaenoic (C20:5), docosahexaenoic (C22:6), and docosapentaenoic (C22:5) acid. The accumulated knowledge has expanded the understanding of the involvement of fatty acids in metabolic processes, thereby enabling the transition from basic exploratory studies to practical issues of application of these biomolecules to CVD treatment. In the future, these findings are expected to facilitate the interpretation and prognosis of changes in metabolic lipid aberrations in CVD.

Changes in the blood fatty-acid profile associated with oxidative-antioxidant disturbances in coronary atherosclerosis.

BACKGROUND: The objective of this work was to study the profile of fatty acids and to search for associations of fatty acids with oxidative-antioxidant parameters and an oxidative-inflammatory biomarker (lipoprotein-associated phospholipase A2) in men with coronary atherosclerosis and coronary heart disease. METHODS: Analysis of 20 fatty acids was performed in 60 men with angiographically confirmed coronary atherosclerosis and coronary heart disease and in a control group of men without coronary heart disease. Serum fatty-acid content was evaluated by high-performance gas-liquid chromatography. The blood levels of oxidative stress, total antioxidative defence, and lipoprotein-associated phospholipase 2 were analyzed. RESULTS: In the group of men with coronary atherosclerosis the levels of myristic and palmitic fatty acids were higher by 59% and 22%, respectively. An increase in the weight percentage of monounsaturated fatty acids was noted, such as palmitoleic, oleic, and octadecenic. Significantly lower levels of polyunsaturated fatty acids, such as linolic, eicosadienoic, eicosatrienoic, arachidonic, eicosapentaenoic, glinolenic, docosapentaenoic, and docosahexaenoic were detected in the group with coronary atherosclerosis. The lipoprotein-associated phospholipase A2 level was higher by 48%. Oxidative stress was higher by 17%, and the total antioxidant defence in serum was lower by 45%. We found correlations between fatty acids and oxidative-antioxidative alterations. The relative risk of vulnerable atherosclerotic plaques correlated with increased levels of palmitic, stearic, oleic, and linolic fatty acids. CONCLUSIONS: Significant alterations in the profile of fatty acids are associated with oxidative-antioxidative alterations and are accompanied by an increase in free-radical formation, which can probably serve as a risk factor of atherosclerosis.

The Role of Secretory Activity Molecules of Visceral Adipocytes in Abdominal Obesity in the Development of Cardiovascular Disease: A Review.

Adipose tissue is considered one of the endocrine organs in the body because of its ability to synthesize and release a large number of hormones, cytokines, and growth and vasoactive factors that influence a variety of physiological and pathophysiological processes, such as vascular tone, inflammation, vascular smooth muscle cell migration, endothelial function, and vascular redox state. Moreover, genetic factors substantially contribute to the risk of obesity. Research into the biochemical effects of molecules secreted by visceral adipocytes as well as their molecular genetic characteristics is actively conducted around the world mostly in relation to pathologies of the cardiovascular system, metabolic syndrome, and diabetes mellitus. Adipokines could be developed into biomarkers for diagnosis, prognosis, and therapeutic targets in different diseases. This review describes the relevance of secretory activity molecules of visceral adipocytes in cardiovascular disease associated abdominal obesity.